Foliations of Isonergy Surfaces and Singularities of Curves

It is well known that changes in the Liouville foliations of the isoenergy surfaces of an integrable system imply that the bifurcation set has singularities at the corresponding energy level. We formulate certain genericity assumptions for two degrees of freedom integrable systems and we prove the opposite statement: the essential critical points of the bifurcation set appear only if the Liouville foliations of the isoenergy surfaces change at the corresponding energy levels. Along the proof, we give full classification of the structure of the isoenergy surfaces near the critical set under our genericity assumptions and we give their complete list using Fomenko graphs. This may be viewed as a step towards completing the Smale program for relating the energy surfaces foliation structure to singularities of the momentum mappings for non-degenerate integrable two degrees of freedom systems.Comment: 30 pages, 19 figure

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23–24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms

Localization and Broadband Follow-Up of the Gravitational-Wave Transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser InterferometerGravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimatesof the time, significance, and sky location of the event were shared with 63 teams of observers covering radio,optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter wedescribe the low-latency analysis of the GW data and present the sky localization of the first observed compactbinary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-rayCoordinates Network circulars, giving an overview of the participating facilities, the GW sky localizationcoverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger,there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadbandcampaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broadcapabilities of the transient astronomy community and the observing strategies that have been developed to pursueneutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-upcampaign are being disseminated in papers by the individual teams

Influence of alcohol consumption and alcohol metabolism variants on breast cancer risk among Black women: results from the AMBER consortium

Background: Moderate to heavy alcohol consumption is associated with an increased risk of breast cancer. The etiologic role of genetic variation in genes involved in ethanol metabolism has not been established, with little information available among women of African ancestry. Methods: Our analysis from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium included 2889 U.S. Black women who were current drinkers at the time of breast cancer diagnosis (N cases = 715) and had available genetic data for four ethanol metabolism genomic regions (ADH, ALDH, CYP2E1, and ALDH2). We used generalized estimating equations to calculate genetic effects, gene* alcohol consumption (≥ 7drinks/week vs. < 7/week) interactions, and joint main plus interaction effects of up to 23,247 variants in ethanol metabolism genomic regions on odds of breast cancer. Results: Among current drinkers, 21% of cases and 14% of controls reported consuming ≥ 7 drinks per week. We identified statistically significant genetic effects for rs79865122-C in CYP2E1 with odds of ER- breast cancer and odds of triple negative breast cancer, as well as a significant joint effect with odds of ER- breast cancer (≥ 7drinks per week OR = 3.92, < 7 drinks per week OR = 0.24, pjoint = 3.74 × 10−6). In addition, there was a statistically significant interaction of rs3858704-A in ALDH2 with consumption of ≥ 7 drinks/week on odds of triple negative breast cancer (≥ 7drinks per week OR = 4.41, < 7 drinks per week OR = 0.57, pint = 8.97 × 10–5). Conclusions: There is a paucity of information on the impact of genetic variation in alcohol metabolism genes on odds of breast cancer among Black women. Our analysis of variants in four genomic regions harboring ethanol metabolism genes in a large consortium of U.S. Black women identified significant associations between rs79865122-C in CYP2E1 and odds of ER- and triple negative breast cancer. Replication of these findings is warranted

Microbial respiration in contrasting ocean provinces via high-frequency optode assays

Microbial respiration is a critical component of the marine carbon cycle, determining the proportion of fixed carbon that is subject to remineralization as opposed to being available for export to the ocean depths. Despite its importance, methodological constraints have led to an inadequate understanding of this process, especially in low-activity oligotrophic and mesopelagic regions. Here, we quantify respiration rates as low as 0.2 µmol O2 L-1 d-1 in contrasting ocean productivity provinces using oxygen optode sensors to identify size-fractionated respiration trends. In the low productivity region of the North Pacific Ocean at Station Papa, surface whole water microbial respiration was relatively stable at 1.2 µmol O2 L-1 d-1. Below the surface, there was a decoupling between respiration and bacterial production that coincided with increased phytodetritus and small phytoplankton. Size-fractionated analysis revealed that cells <5 µm were responsible for the majority of the respiration in the Pacific, both at the surface and below the mixed layer. At the North Atlantic Porcupine Abyssal Plain, surface whole water microbial respiration was higher (1.7 µmol O2 L-1 d-1) than in the Pacific and decreased by 3-fold below the euphotic zone. The Atlantic size-fraction contributions to total respiration shifted on the order of days during the evolution of a phytoplankton bloom with regular storm disturbances. The high-resolution optode method used in the Atlantic captured these significant shifts and is consistent with coinciding stain-based respiration methods and historical site estimates. This study highlights the dynamic nature of respiration across vertical, temporal, and size-fractionated factors, emphasizing the need for sensitive, high-throughput techniques to better understand ocean ecosystem metabolism

Genetic variants in anti-Müllerian hormone-related genes and breast cancer risk: results from the AMBER consortium

Purpose: Circulating anti-Müllerian hormone (AMH) levels are positively associated with time to menopause and breast cancer risk. We examined breast cancer associations with single nucleotide polymorphisms (SNPs) in the AMH gene or its receptor genes, ACVR1 and AMHR2, among African American women. Methods: In the AMBER consortium, we tested 65 candidate SNPs, and 1130 total variants, in or near AMH, ACVR1, and AMHR2 and breast cancer risk. Overall, 3649 cases and 4230 controls contributed to analyses. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were calculated using multivariable logistic regression. Results: After correction for multiple comparisons (false-discovery rate of 5%), there were no statistically significant associations with breast cancer risk. Without correction for multiple testing, four candidate SNPs in ACVR1 and one near AMH were associated with breast cancer risk. In ACVR1, rs13395576[C] was associated with lower breast cancer risk overall (OR 0.84; 95% CI 0.72, 0.97) and for ER+ disease (OR 0.75; CI 0.62, 0.89) (p < 0.05). Rs1220110[A] and rs1220134[T] each had ORs of 0.89–0.90 for postmenopausal and ER+ breast cancer (p ≤ 0.03). Conversely, rs1682130[T] was associated with higher risk of ER+ breast cancer (OR 1.17; 95% CI 1.04, 1.32). Near AMH, rs6510652[T] had ORs of 0.85–0.90 for breast cancer overall and after menopause (p ≤ 0.02). Conclusions: The present results, from a large study of African American women, provide limited support for an association between AMH-related polymorphisms and breast cancer risk and require replication in other studies

Local Search is Underused in Genetic Programming

Trujillo, L., Z-Flores, E., Juárez-Smith, P. S., Legrand, P., Silva, S., Castelli, M., ... Muñoz, L. (2018). Local Search is Underused in Genetic Programming. In R. Riolo, B. Worzel, B. Goldman, & B. Tozier (Eds.), Genetic Programming Theory and Practice XIV (pp. 119-137). [8] (Genetic and Evolutionary Computation). Springer. https://doi.org/10.1007/978-3-319-97088-2_8There are two important limitations of standard tree-based genetic programming (GP). First, GP tends to evolve unnecessarily large programs, what is referred to as bloat. Second, GP uses inefficient search operators that focus on modifying program syntax. The first problem has been studied extensively, with many works proposing bloat control methods. Regarding the second problem, one approach is to use alternative search operators, for instance geometric semantic operators, to improve convergence. In this work, our goal is to experimentally show that both problems can be effectively addressed by incorporating a local search optimizer as an additional search operator. Using real-world problems, we show that this rather simple strategy can improve the convergence and performance of tree-based GP, while also reducing program size. Given these results, a question arises: Why are local search strategies so uncommon in GP? A small survey of popular GP libraries suggests to us that local search is underused in GP systems. We conclude by outlining plausible answers for this question and highlighting future work.authorsversionpublishe

Association of Age, Antipsychotic Medication, and Symptom Severity in Schizophrenia With Proton Magnetic Resonance Spectroscopy Brain Glutamate Level: A Mega-analysis of Individual Participant-Level Data.

Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear. To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites. The MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data. In total, 45 1H-MRS studies contributed data. Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor. Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL). In total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F1,1211.9 = 4.311, P = .04) and Glx (F1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4 = 47.533, P &lt; .001; cerebrospinal fluid-corrected Glu, F1,1216.7 = 5.610, P = .02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, -0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose. Findings from this mega-analysis suggest that lower brain Glu levels in patients with schizophrenia may be associated with antipsychotic medication exposure rather than with greater age-related decline. Higher brain Glu levels may act as a biomarker of illness severity in schizophrenia

Tissue graft rejection in mice

A liver-slice to kidney-bed grafting system was used to study the course of rejection of a specific tissue across various genetic barriers in inbred strains of mice. Rejection or survival, scored histologically at various times after grafting, demonstrated that multiple non H-2 differences cause rejection at least as rapidly as H-2 differences. Differences at the K end of the mouse major histocompatibility complex cause tissue rejection more rapidly than do differences at the D end of the complex. The latter differences cause chronic rejection similar to that found across several minor H locus barriers. The H-2 haplotype carried by the recipient or the strength of the H-2 antigens of the donor affect the survival time in liver tissue grafts. Studies employing this model system will contribute to the definition of different immunogenetic parameters affecting survival of various tissues in a genetically well-defined animal model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46746/1/251_2005_Article_BF01576941.pd

The differential diagnosis of chronic daily headaches: an algorithm-based approach

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review